Process for isomerizing 8alpha-methyl-1, 2, 3, 4, 6, 7, 8, 8alpha-octahydro-1-ethynyl-1beta-hydroxy-6-oxonaphthalene and isomer obtained thereby



Melvin S. Newman, Columbus, Ohio, and Sambasiva Swaminathan, Mylapore,India, assignors to The Ohio State University Research Foundation,Columbus, Ohio, a corporation of Ohio No Drawing. Application March 8,1954 Serial No. 414,885

3 Claims. (Cl. 260-586) This application is a continuation-in-part ofour application Serial No. 267,097, filed January 18, 1952, nowabandoned, which is a continuation-in-part of our application Serial No.242,982, filed August 21, 1951, and now Patent No. 2,614,123. Theinventions disclosed in this application relate to new compositions ofmatter and to methods for their preparation.

One object of this invention is to produce a new composition of matterconsisting of 1-acetyl-6-oxo-8a-methyl-3,4,6,7,8,8a-hexahydronaphthalene, and 8a-methy1-1,2,3,-4,6,7,8,8a-octahydro-l-ethynyl-la-hydroxy 6 oxonaphthalene. The1-acetyl-6-oxo-8a-methyl-3,4,6,7,8,8m-hexahydronaphthalene can beconverted to cortisone according to the procedure disclosed in U. S;Patent 2,673,872, or according to the procedure disclosed'by Friedmannet a1. [Chemistry and Industry, September 15, 1951, pp. 777-778]. TheSet-methyl-1,2,3,4,6,7,8,8a-octahydro-1-ethynyl-1a-hydroxy-6-oxonaphthalene produced by the process of thepresent invention can be converted to thel-acetyl-6-oxo-8a-methyl-3,4,6,7,8,8a hexahydronaphthalene by refluxingin formic acid. The 8a-methyl-1,2,3,- 4,6,7,8,8u-octahydro 1ethynyl-1a-hydroxy-6-oxonaphthalene can also be converted to an activeinsecticide by reacting with a halogenated organic acid, e. g.,monochloroacetic acid, and reacting the product produced thereby with ametal thiocyanate, e. g., potassium thiocyanate. The compounds producedby the present invention are also useful as plant growth regulators.

The starting compound for the process of the present invention isSet-methyl-1,2,3,4,6,7,8,8a-octahydro-1-ethynyl-lp-hydroxy-6-oxonaphthaleneand the process of making it is disclosed in application for UnitedStates Patent Serial No. 414,886, filed March 8, 1954, now Patent No.2,714,615. In order to produce the new compositions of matter of thepresent invention, we react the above described starting material withformic acid by dissolving it in formic acid and refluxing. The startingcompound as stated in said copending application has a formula asfollows:

CECH

Also as stated in said copending application Serial No. 414,886, thecompound has a melting point at 171.5- 172.5 and was analyzed to have C,76.3-76.4 and H, 7.8. The above starting compound is considered as thefiepimer and based on the analogy to configurations that have beenascribed to ethynyl alcohols prepared from 17-keto steroids, isconsidered to have the valence bond of the hydroxyl group above theplane of the paper.

ats. Patent ice . 2 v The acetyl compound has a formula as follows:

It will be noted that not only are the ethynyl andhydroxyl radicals (i.e. OH 05011) converted into the acetyl radical but also the 1 and 2carbons become unsaturated through the introduction of a double bondbetween them.

Wehave found that by the use of our process not only do we. produce the1.-acetyl compound which is the main object of our process, but we alsoproduce an isomer thereof which is also an epimer of the startingcompound having a melting point at 145-146 degrees centigrade. In linewith our assumptions above in regard to the ,8 starting compound, wedesignate the new epimer as an t! compound and ascribe'a configurationin which the hydroxyl group is below theplane of the paper.

Following are examples of the process we have used to produce our novelcompositions of matter:

Example 1 .1-acetyl-6-0x0-8a-methyl-3,4,6,7,8,8u-hexahydronaphthalene OC Ha A solution ofSat-methyl-l,2,3,4,6,7,8,8a-octahydro-lethynyl-l-B-hydroxy 6oxonaphthalene (melting point 171-172 degrees, 2.8 grams) in formic acid(92 percent; 16 milliliters) was refluxed for two hours. The reactionmixture was then poured into water and the aqueous suspension extractedwith ether twice. The ether extract after successive washings withdilute sodium hydroxide solution, water and saturated sodium chloridesolution was dried over anhydrous sodium sulfate and later concentrated.A brown viscous residue remained and was chromatographed on a column ofdeactivated alumina (Fisher) prepared by treatment with methanol andsubsequent drying for 6 hours at 130 degrees.

The reaction product was dissolved in dry benzene (100 milliliters) andpassed through the column. After most of the benzene had passed through,the column was eluted with ether (200 milliliters) and the ethersolution concentrated. A viscous liquid remained and solidified oncooling. The solid was crystallized from ether; melting point -93degrees. A recrystallization from ether yielded the desired acetylcompound having the formula shown above, melting at 92-93 degreescentigrade and exhibiting the following characteristics.

Ultra-violet spectrum:

Max

3 Analysis.-Calculated for C H O C, 76.4; H, 7.9. Found: C, 76.7; H,8.0.

Example 2.-8a-mefhyl-1,2,3,4,6,7,8,8m-0ctahydr0- I-ethyny l-1a-hydroxy-6-oxonaphthalene A solution of 4.5 grams ofSon-methyl-l,2,3,4,6,7,8,8aoctahydro-1-ethynyl-1-13-hydroxy-6-oxonaphthalene(melting point 171-172 degrees eentigrade) in 92 percent formic acid (20milliliters) was fluxed gently for one hour. At the end of this period,the excess formic acid was removed by distillation under reducedpressure. The

dark brown residue was taken up in ether (150 milliliters) iAnalysis.Calculated for C H O C, 76.4; H, 7.9. Found: C, 76.1, 76.3; H,7.6, 7.7.

The ethynyl alcohol, described above, furnished a red2,4-dinitrophenylhydrazone which after a crystallization from ethanolmelted at 195-198 degrees.

Analysis.-Calc. for C I-1 N 0 C, 59.4; H, 5.3; N, 14.6. Found: C, 59.3;H, 5.4; N, 14.6.

It is to be understood that modifications of this compound coming withinthe scope of the invention are intended to be. covered by the claimshereof.

We claim:

1. A composition of matter consisting ofSoc-methyll,2,3,4,6,7,8,8u-octahydro 1ethynyl-la-hydroxy-6-oxonaphthalene having a melting point of 145-146degrees centigrade.

2. A process of producing an 8a-methyl-l,2,3,4,6,7,8,- Sa-Qctahydro 1ethynyl-la-hydroxy-6-oxonaphthalene which comprises refluxing a solutionof 8a-methyl-1,2,3,- 4,6,7,8,8a octahydro l ethynyl-l8-hydroxy-6-oxonaphthalene in formic acid and separating8a-methyl-1,2,3,4,- 6,7,8,8aoctahydro-l-ethynyl-1a-hydroxy-6-oxonaphthalene from the reflux mixture.

3. A process for isomerizingBot-methyl-l,2,3,4,6,7,8,8aoctahydro-l-ethynyl-I/B-hydroxy-6-oxonaphthalenewhich comprises refluxing a solution of said compound in formic acid andseparating8a-methyl-1,2,3,4,6,7,8,8aoctahydro-1-ethynyl-1a-hydroxy-6-oxonaphthalenehaving a melting point of about 145l46 degrees centigrade.

References Cited in the file of this patent UNITED STATES PATENTS Newmanet al Oct. 14, 1952 Newman et al Mar. 30, 1954 OTHER REFERENCES

1. A COMPOSITION OF MATTER CONSISTING OF8A-METHYL1,2,3,4,6,7,8,8A-OCTAHYDRO - 1 -ETHYNYL-1A-HYDROXY-6-OXONAPHTHALENE HAVING A MELTING POINT OF 145-146DEGREES CENTIGRADE.